A recent Mendelian randomization study published in the journal Circulation: Cardiovascular Genetics found that genetically low vitamin D levels were not associated with increased risk of coronary artery disease (CAD).

CAD, also known as heart disease, is the leading cause of death in the United States. It occurs when cholesterol-containing deposits, called plaques, begin to develop in the coronary arteries. The plaque buildup narrows the coronary arteries, which reduces blood flow to the heart. As a result, chest pain, shortness of breath, irregular heartbeat and light-headedness are common symptoms. In some cases, the artery can become completely blocked, causing a heart attack.

Observational studies have suggested that low vitamin D levels are associated with an increased risk of CAD-related events. Therefore, researchers have become interested in whether vitamin D supplementation may play a role in the prevention of mortality and morbidity due to CAD. Researchers recently sought to find this out by conducting a Mendelian randomization study.

Mendelian randomization studies possess the ability to prove causation, similar to a randomized controlled trial (RCT). Instead of randomly dividing study participants into two groups, the control and experimental groups, Mendelian randomization utilizes nature’s randomization of genes. In this study, the researchers assessed the genotypes of 22,233 individuals with CAD and 64,762 individuals without CAD, searching for individuals who have genetic variants that are associated with low levels of vitamin D. The researchers found that individuals who were genetically predisposed to low vitamin D levels had the same risk for developing CAD as those who were not predisposed (OR 0.99, p = 0.93).

The researchers summarized their findings,

“…Our study provides evidence against a causal role for vitamin D in CAD susceptibility.”

They went on to state,

“These findings suggest that previous observational epidemiologic associations may have been influenced by confounding or reverse causation.”

While these findings conflict with observational studies, they are consistent with a previous Mendelian randomization study’s results. The previous study determined that low vitamin D levels were related to increased all-cause mortality and cancer mortality, but not cardiovascular mortality.

The recent study possessed several strengths worth recognizing. As mentioned earlier, a Mendelian randomization study has the ability to prove causation, making it one of the strongest study designs. Furthermore, the study used a large population sample. Lastly, the study’s results represent the relationship of a life-long exposure to reduced vitamin D levels. Since vitamin D is unable to be patented as many medications are, long-term RCTs on the effects of vitamin D on CAD are unavailable.

This study looked at people with genes associated with lower vitamin D levels. While in most people lower vitamin D implies less sunlight, we have no information about sun exposure in this study.

Since vitamin D is only one of a number of effects of sunlight exposure perhaps it is one of the other ones that influences CAD.

On the other hand, given that these people had genetically lower vitamin D it is also possible that there are other compensating alleles that make this lower level of vitamin D more effective. An example might be an allele that increased binding affinity for vitamin D so that the net impact is the same as a higher level in someone else.